Rewriting Life

In CRISPR Fight, Co-Inventor Says Broad Institute Misled Patent Office

New evidence in the battle to control a gene-editing technology that is worth billions.

A junior scientist formerly employed by the Broad Institute says the storied MIT-Harvard institution’s claim to have invented CRISPR gene editing isn’t accurate, and that the organization misled the patent office.

The former graduate student, Shuailiang Lin, made his accusations in an e-mail sent to Jennifer Doudna, a professor at the University of California, Berkeley, who is Broad’s chief rival for scientific and commercial credit to CRISPR.

In the e-mail, sent on February 28, 2015, Lin called the Broad’s claims “a joke” and “unfair to me and [to] science history.” He went on to say, “I will try to defend the truth.”

The explosive e-mail appears among a deluge of legal filings made public this week by the U.S. Patent Office as part of a high-stakes dispute between Broad and Berkeley to control the intellectual property in CRISPR, a powerful way of altering the DNA inside living cells that’s already worth billions.

Doudna and collaborators in Europe published a key paper on the system in 2012, but Broad was able to win more than a dozen patents by telling the patent office that Feng Zhang, a researcher there, had quietly made key inventions months earlier.

Lin’s account is striking not only because he worked in Zhang’s lab at the time but because he is listed as an inventor on Broad’s earliest patent filing, from December 2012.

The e-mail was sent as part of a job request to Doudna. In it, Lin, who is from China, seemed ready to barter inside information and assistance with the patent case in exchange for a job. “I am willing to give more details and records if you are interested or whoever is interested to clear the truth,” he said.

Lin says that in late 2011 he was the only lab member working on CRISPR and that the lab was not then able to make the technique work, something he says he can document with lab notebooks, e-mails, and results that “recorded every step of the lab’s failure process.”

“I think a revolutionary technology like this … should not be mis-patented. We did not work it out before seeing your paper, it’s really a pity,” he wrote to Doudna. “But I think we should be responsible for the truth. That’s science.”

Lin is currently employed as a postdoctoral researcher at the University of California, San Francisco. He did not respond to repeated attempts to contact him by phone and e-mail.

CRISPR has already attracted hundreds of millions in investments by government agencies, through stock offerings and IPOs, and by way of alliances with makers of biotech plants and human drugs. It has also generated multimillion-dollar stock windfalls for key scientists, including Doudna and Broad’s Zhang.

The e-mail was submitted to the U.S. Patent Office by lawyers for Berkeley and is one of scores of documents filed this week to support motions ahead of an administrative trial, called an interference, that will determine who ends up with the patent rights. The crucial question is exactly who made key inventions and when.

Most researchers directly involved are keeping mum or signing affidavits backing their institutions’ versions of events. Indeed, in May 2014 Lin also signed such an oath in connection with one of Broad’s patent applications. That statement—which carries legal penalties if found to be false—could be seen as contradicting the charges he made to Doudna a year later.

In Broad’s various legal filings, which stretch across a score of pending patents, either Lin’s name is mostly absent or he is portrayed as a minor figure with limited autonomy—under the “intellectual control” of Zhang, the lab’s chief, and not necessarily aware of other doings in the lab.

Lin worked in the Zhang lab for nine months starting in October 2011, the crucial period during which Broad says it mastered CRISPR gene editing in human cells. He later took a post at the Harvard laboratory of biologist Norbert Perrimon.

In an interview, Perrimon said Lin was a productive scientist and there were no red flags concerning his behavior. “I never had any issues with him,” he says. “I think that people will have to look at this statement carefully.”

Other Broad researchers are not willing to discuss what occurred in the lab. Neville Sanjana, a biologist who now holds a faculty position at the New York Genome Center, shared a lab bench with Lin during the critical period and oversaw part of his work. Sanjana declined to comment on Lin’s claims or character and referred questions to the Broad Institute.

Lee McGuire, a spokesperson for the Broad, cast doubt on Lin’s motivations, saying he had been rejected for a new post at the Cambridge institution immediately before firing off the e-mail to Doudna. He said that Lin, whose position in the Perrimon lab was ending, was in a rush to renew his visa, something he was able to do after being offered a position at UCSF.

“Abundant evidence already shows that the student’s claims are false,” says McGuire.

The patent fight hinges on who will control commercial rights to editing in human cells. Berkeley says it should control those rights because of a key paper published in 2012 by Doudna and Emmanuel Charpentier, a researcher in Europe, showing a simplified CRISPR system able to cut DNA in vitro, or in a test tube.

Berkeley’s lawyers say other scientists, including those at the Broad Institute, quickly jumped on that finding in order to demonstrate that it could also work in human cells, where its application is most valuable because of the possibility of creating new types of gene-therapy treatments.

In his e-mail to Doudna, Lin agreed with Berkeley’s version of events. “After seeing your in virto [sic] paper, Feng Zhang and Le Cong quickly jumped to the project without letting me know,” Lin complained. Cong is another scientist in the lab whose results are especially important to Broad’s case.

The Broad Institute, however, was exploring CRISPR well before Doudna’s paper. Not only was Lin assigned to work on it by 2011, but Zhang submitted a grant application to the National Institutes of Health in January 2012 in which he asked the agency to finance a larger effort to turn CRISPR into an editing tool.

Despite Doudna’s earlier publication, Broad was able to get its patents after it told the patent office that its effort to edit human cells had been successful, even though details were not published until 2013.

The documents in the interference proceeding show the sides are well matched. Broad has made clever scientific arguments as to why Berkeley’s test-tube research never amounted to a true, patentable invention. Berkeley, for its part, argues that Broad’s Zhang was just one of the scientists who grabbed on to its discovery.

The patent battle is becoming costly. During a conference call this month, Katrine Bosley, the CEO of Editas Medicine, a startup cofounded by Zhang that licensed the Broad patents, said she was very confident they would hold up. In its most recent corporate filings, Editas said it had spent $10.9 million so far this year in legal fees to defend the patents.

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